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OPTICAL ISOMERISM

R W Grime Ripon Grammar School

Molecular mirror images

Optical isomerism and chirality Enantiomers and racemates

Self-Test: recognising optical isomers from structural formulae

Polarimetry: recognising optical isomers by experiment

Examples of optical isomers and their importance

thalidomide carvone limonene

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• All molecules have a mirror image – but for most molecules it is the same molecule.

fluoromethane

H

CH F

H

H

CHF

H

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• For some molecules the mirror image is a different molecule (the mirror image is non-superimposable).

OH

CH CH3

COOH

OH

CHH3C

HOOC

(-) lactic acid (+) lactic acidin sour milk in muscles

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• Left and right hands are an example of non-superimposable mirror images.

5• This usually happens when a molecule contains a C atom with four different groups attached (chiral / asymmetric C).

• Such molecules are said to be chiral or optically active.

a

Cb c

d

a

Cbc

d

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• The optical isomers are called enantiomers.

• These are distinguished by +/-, D/L or more correctly R/S.

• A 50/50 mixture of the two enantiomers is called a racemic mixture or a racemate.

7TASK Some of the following molecules

are optically active. For each one, click its name below and decide whether it is optically active or not. Click again to see if you are correct.

a) propan-2-ol

b) 2-chlorobutane

c) 1-chlorobutane

d) 3-methylhexane

e) butanone

f) 2-methylbutanoic acid

g) butan-2-ol

h) 1-chloro-3-methylpentane

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propan-2-ol

NOT OPTICALLY ACTIVE

CH3 CH CH3

OH

Click here to go back to the optical isomerism task

92-chlorobutane CH3 CH CH2 CH3

Cl

OPTICALLY ACTIVE

CH2CH3

CH Cl

CH3

CH2CH3

CHCl

H3C

Click here to go back to the optical isomerism task

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1-chlorobutane

NOT OPTICALLY ACTIVE

CH2 CH2 CH2 CH3

Cl

Click here to go back to the optical isomerism task

113-methylhexane CH2 CH CH2 CH2

CH3

CH3CH3

OPTICALLY ACTIVE

CH2CH2CH3

CH CH2CH3

CH3

CH2CH2CH3

CHCH3CH2

CH3

Click here to go back to the optical isomerism task

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butanone

NOT OPTICALLY ACTIVE

C CH2 CH3CH3

O

Click here to go back to the optical isomerism task

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propan-2-ol CH3 CH CH3

OH

NOT OPTICALLY ACTIVE

Click here to go back to the optical isomerism task

142-methylbutanoic acid

CH3 CH2 CH

CH3

C

O

OH

OPTICALLY ACTIVE

CH2CH3

CCH3 COOH

H

CH2CH3

CCH3

HHOOC

Click here to go back to the optical isomerism task

15butan-2-ol

CH3 CH2 CH

OH

CH3

OPTICALLY ACTIVE

CH2CH3

CCH3 OH

H

CH2CH3

CCH3

HHO

Click here to go back to the optical isomerism task

161-chloro-3-methylpentane

CH3 CH2 CH

CH3

CH2 CH2

Cl

OPTICALLY ACTIVE

CH2CH3

CCH3 CH2CH2Cl

H

CH2CH3

CCH3

HCH2ClCH2

Click here to go back to the optical isomerism task

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• Molecules that are optical isomers are called enantiomers.

• Enantiomers have identical chemical and physical properties, except:

• Their effect on plane polarised light;

• Their reaction with other chiral molecules

18• Light is a form of electromagnetic radiation.

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normal light(waves vibrate in all directions)

plane-polarised light(vibrates in only one direction)

plane-polarised light after clockwise rotation

• The wave vibrations are perpendicular to the direction of travel of the wave.

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• Optical isomers rotate the plane of plane polarised light.

(-)-enantiomer(anticlockwise rotation)

(±)-racemate(no overall effect)

(+)-enantiomer(clockwise rotation)

21POLARIMETERS can be used to analyse the effect optical isomers have on plane polarised light:

Heriot Watt University has a web page with an interactive tutorial and self-test questions about this topic: http://scholar.hw.ac.uk/site/chemistry/activity5.asp?outline

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• Chiral molecules often react differently with other chiral molecules.

• This is like the idea that a right hand does not fit a left handed glove – the molecule must be the correct shape to fit the molecule it is reacting with.

• Many natural molecules are chiral and most natural reactions are affected by optical isomerism.

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• For example, most amino acids (and so proteins) are chiral, along with many other molecules.

• In nature, only one optical isomer occurs (e.g. all natural amino acids are rotate polarised light to the left).

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• Many drugs are optically active, with one enantiomer only having the beneficial effect.

• In the case of some drugs, the other enantiomer can even be harmful, e.g. thalidomide.

25• In the 1960’s thalidomide was given to pregnant women to reduce the effects of morning sickness.

• This led to many disabilities in babies and early deaths in many cases.

The photographs are both from ‘Molecule of the Month’ at Bristol University: http://www.chm.bris.ac.uk/motm/thalidomide/start.html

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H2CCH2

C

NHO O

H

N

O

O

H2CCH2

C

NH OO

H

N

O

O

S thalidomide (effective drug)

The body racemises each enantiomer, so even pure S is

dangerous as it converts to R in the body.

R thalidomide (dangerous drug)

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• Thalidomide was banned worldwide when the effects were discovered.

• However, it is starting to be used again to treat leprosy and HIV.

• Its use is restricted though and patients have to have a pregnancy test first (women!) and use two forms of contraception (if sexually active).

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S carvone (caraway seed) R carvone (spearmint)

O

CH3

H C CH2

H3C

O

CH3

HCH2C

CH3

Caraway Seed has a warm, pungent, slightly bitter flavour with aniseed overtones.

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S limonene (lemons) R limonene (oranges)

CH3

HCCH2

CH3

CH3

H C CH2

H3C